Functional responses of human neonatal B lymphocytes to antigen receptor cross-linking and CpG DNA

Human neonates are immunologically immature and consequently are highly susceptible to infection. The cellular basis for the dysfunctional immune responses of neonates is not clear, but is likely to reflect the immaturity of both B and T cell populations. Here we have examined the ability of human cord blood B cells to respond to antigen receptor cross-linking and also to CpG containing oligodeoxynucleotides (ODN), and compared their responses with those of adult peripheral blood B cells. Antigen receptor cross-linking with soluble F(ab')2 anti-IgM antibodies, induced HLA-DR and CD86 up-regulation and proliferation to a similar extent in adult and cord blood B cells. Both interleukin (IL)-2 and IL-4 co-stimulated anti-IgM-induced proliferation, but cord blood B cells were less sensitive than adult B cells to the co-stimulatory effects of IL-2. Antigen receptor cross-linking induced secretion of the chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta in adult and cord blood B cells, and secretion was enhanced by IL-2 or IL-4. CpG-ODN induced up-regulation of HLA-DR and CD86 expression and proliferation of adult and cord blood B cells, and anti-IgM and CPG-ODN synergized in the induction of proliferation. CpG-ODN also induced MIP-1 alpha and MIP-1 alpha secretion in adult and cord blood B cells. In addition to functional studies we examined the expression of CD62L (l-selectin), CCR7 and CXCR5. Our data show that surface expression of CD62L and CCR7 is lower on cord blood B cells than on adult B cells, suggesting that human cord blood B cells may exhibit homing defects.